Synthesis And Antitumor Activity Of N-aryl Indolones Derivatives

Indoleheterocyclic structure is widely presented in many nature products and drug molecules. Indoleketone is a kind of indole derivatives which possess a wide range of biological activities such as anti-tumor, antibacterial, antifungal, antiviral, anti-HIV and central nervous system modulating activity. In the past, many researches have been focused on the synthesis and biological evaluation of the 1-substituted,3-substituted and 5-substituted indolone derivatives, however, there are still lack of study on the 1,3,5-di-substituted or 1,3,5-tri-substituted indolone derivatives. Therefore, this thesis has studyed the synthetic route and bioactivity of 1,3,5-di-substituted or 1,3,5-tri-substituted indolone derivatives.In this thesis, the 4-bromoanilines or isatin(Indolones) was used as the starting material for the N-1 aryl-substitution and then Huang-Ming-Long reduction, which was followed by aldolcondensation to the 3-carbonyl group and then Suzuki or Heck coupling reaction to the 5 position.78 novel target compounds were synthesized and 52 target compounds which never been reported in literatures were designed and synthesized, and the 52 target structures were confirmed by 1H NMR,1C NMR.In this thesis,58 target compounds were evaluated for their anticancer activities by MTT method with three kinds of cancer cells:human hepatoma cell HepG2, human leukemia cell K562 and human colon cancer cell HT-29. MTT test results revealed that the isatins’ 3-benzylidyn substitution could enhance their potency. Moreover, the 5-bromo substituted target compounds exhibited significantly improved activity when comparing to their 5-H counterparts. Meanwhile the N-1 aryl-substitution could maintain or increase the activities. Among those targets,5-bromo-1-(4-methoxyphenyl)-3-(4-(trifiuoromethyl) benzylidene)indolin-2-one exhibited the best antitumor activity with IC50 values of 0.04μM,0.33μM and 0.13μM against K562, HepG2 and HT-29, respectively.